ADT4_MACFA
ID ADT4_MACFA Reviewed; 315 AA.
AC Q4R8M0;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=ADP/ATP translocase 4 {ECO:0000305};
DE AltName: Full=ADP,ATP carrier protein 4 {ECO:0000250|UniProtKB:Q3V132};
DE AltName: Full=Adenine nucleotide translocator 4 {ECO:0000250|UniProtKB:Q3V132};
DE Short=ANT 4 {ECO:0000250|UniProtKB:Q3V132};
DE AltName: Full=Solute carrier family 25 member 31 {ECO:0000305};
GN Name=SLC25A31 {ECO:0000250|UniProtKB:Q9H0C2};
GN ORFNames=QtsA-12102 {ECO:0000303|Ref.1};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: ADP:ATP antiporter that mediates import of ADP into the
CC mitochondrial matrix for ATP synthesis, and export of ATP out to fuel
CC the cell (By similarity). Cycles between the cytoplasmic-open state (c-
CC state) and the matrix-open state (m-state): operates by the alternating
CC access mechanism with a single substrate-binding site intermittently
CC exposed to either the cytosolic (c-state) or matrix (m-state) side of
CC the inner mitochondrial membrane (By similarity). Specifically required
CC during spermatogenesis, probably to mediate ADP:ATP exchange in
CC spermatocytes. Large ATP supplies from mitochondria may be critical for
CC normal progression of spermatogenesis during early stages of meiotic
CC prophase I, including DNA double-strand break repair and chromosomal
CC synapsis. In addition to its ADP:ATP antiporter activity, also involved
CC in mitochondrial uncoupling and mitochondrial permeability transition
CC pore (mPTP) activity (By similarity). Plays a role in mitochondrial
CC uncoupling by acting as a proton transporter: proton transport
CC uncouples the proton flows via the electron transport chain and ATP
CC synthase to reduce the efficiency of ATP production and cause
CC mitochondrial thermogenesis. Proton transporter activity is inhibited
CC by ADP:ATP antiporter activity, suggesting that SLC25A31/ANT4 acts as a
CC master regulator of mitochondrial energy output by maintaining a
CC delicate balance between ATP production (ADP:ATP antiporter activity)
CC and thermogenesis (proton transporter activity). Proton transporter
CC activity requires free fatty acids as cofactor, but does not transport
CC it (By similarity). Also plays a key role in mPTP opening, a non-
CC specific pore that enables free passage of the mitochondrial membranes
CC to solutes of up to 1.5 kDa, and which contributes to cell death. It is
CC however unclear if SLC25A31/ANT4 constitutes a pore-forming component
CC of mPTP or regulates it (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P48962, ECO:0000250|UniProtKB:Q3V132}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP(in) + ATP(out) = ADP(out) + ATP(in); Xref=Rhea:RHEA:34999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P48962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:P48962};
CC -!- ACTIVITY REGULATION: The matrix-open state (m-state) is inhibited by
CC the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open
CC state (c-state) is inhibited by the membrane-impermeable toxic
CC inhibitor carboxyatractyloside (CATR) (By similarity). Proton
CC transporter activity is inhibited by ADP:ATP antiporter activity (By
CC similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P48962}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P02722}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P02722}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:Q9H0C2}; Multi-pass
CC membrane protein {ECO:0000255}. Cell projection, cilium, flagellum
CC membrane {ECO:0000250|UniProtKB:Q3V132}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In sperm flagellum this protein is located in the
CC fibrous sheath, a non-mitochondrial region (By similarity). May
CC localize to non-mitochondrial membranes (By similarity).
CC {ECO:0000250|UniProtKB:Q9H0C2}.
CC -!- DOMAIN: The transmembrane helices are not perpendicular to the plane of
CC the membrane, but cross the membrane at an angle. Odd-numbered
CC transmembrane helices exhibit a sharp kink, due to the presence of a
CC conserved proline residue. {ECO:0000250|UniProtKB:P02722}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AB168432; BAE00552.1; -; mRNA.
DR RefSeq; NP_001274602.1; NM_001287673.1.
DR AlphaFoldDB; Q4R8M0; -.
DR SMR; Q4R8M0; -.
DR STRING; 9541.XP_005555943.1; -.
DR Ensembl; ENSMFAT00000011776; ENSMFAP00000037526; ENSMFAG00000000529.
DR GeneID; 102143674; -.
DR CTD; 83447; -.
DR VEuPathDB; HostDB:ENSMFAG00000038000; -.
DR eggNOG; KOG0749; Eukaryota.
DR GeneTree; ENSGT00390000001301; -.
DR OMA; AHCWLVI; -.
DR OrthoDB; 870903at2759; -.
DR Proteomes; UP000233100; Chromosome 5.
DR Bgee; ENSMFAG00000000529; Expressed in pituitary gland and 13 other tissues.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR GO; GO:0005471; F:ATP:ADP antiporter activity; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007141; P:male meiosis I; ISS:UniProtKB.
DR GO; GO:0140021; P:mitochondrial ADP transmembrane transport; IEA:InterPro.
DR GO; GO:1990544; P:mitochondrial ATP transmembrane transport; IEA:InterPro.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002113; ADT_euk_type.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR PANTHER; PTHR45635; PTHR45635; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00927; ADPTRNSLCASE.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 2: Evidence at transcript level;
KW Antiport; Cell membrane; Cell projection; Cilium; Differentiation;
KW Flagellum; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Repeat; Spermatogenesis; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..315
FT /note="ADP/ATP translocase 4"
FT /id="PRO_0000297625"
FT TOPO_DOM 1..19
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 20..49
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 50..86
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 87..111
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 112..121
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 122..142
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 143..190
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 191..211
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 212..222
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 223..243
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 244..283
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 284..301
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 302..315
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT REPEAT 18..110
FT /note="Solcar 1"
FT REPEAT 123..213
FT /note="Solcar 2"
FT REPEAT 220..307
FT /note="Solcar 3"
FT REGION 247..252
FT /note="Important for transport activity"
FT /evidence="ECO:0000250|UniProtKB:P12235"
FT MOTIF 247..252
FT /note="Nucleotide carrier signature motif"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 92
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 104
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 247
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
SQ SEQUENCE 315 AA; 35075 MW; F7D488B62760C9A6 CRC64;
MHREPPKKKA EKRLFDASSF GKDLLAGGVA AAVSKTAVAP IERVKLLLQV QASSKQISPE
ARYKGMVDCL VRIPREQGFF SFWRGNLANV IRYFPTQALN FAFKDKYKQL FMSGVNKEKQ
FWRWFLANLA SGGAAGATSL CVVYPLDFAR TRLGVDIGKG PEERQFKGLG DCIMKIAKSD
GIAGLYQGFG VSVQGIIVYR ASYFGAYDTV KGLLPKPKKT PFLVSFFIAQ VVTTCSGILS
YPFDTVRRRM MMQSGEAKRQ YKGTLDCFVK IYQHEGINSF FRGAFSNVLR GTGGALVLVL
YDKIKEFFHI DIGGR
